The purpose of this study was to investigate the prognostic value of percentage variation of metabolic tumor burden in patients with head and neck squamous cell carcinoma (HNSCC). Patients referred to undergo (18) fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT for staging of HNSCC were included in this study. Using a dual-phase method, standardized uptake value maximum (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded and respectively used to calculate retention index (RI), %ΔMTV, and %ΔTLG. Recurrence-free survival (RFS) was determined by Kaplan-Meier method and compared with studied PET parameters in univariate and multivariate. Seventy patients (61 men/9 women; 62.9 ± 9.1 years old) were included. In univariate, SUVmax, RI, MTV, and TLG (p ≤ .0001) were significantly correlated with RFS, unlike %ΔMTV (p = 137) and %ΔTLG (p = .517). In multivariate, RI (p = .005) and MTV (p = .022) persisted as independent prognostic factors. Our results did not prove a prognostic interest of percentage variation of metabolic tumor burden in patients with HNSCC but confirmed that RI and MTV are independently correlated with RFS. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.